Jump to main content
Jump to site search

Issue 16, 2015
Previous Article Next Article

Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn2+-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate

Author affiliations

Abstract

Although involved in various physiological functions, nucleoside bis-phosphate analogues and their metal-ion complexes have been scarcely studied. Hence, here, we explored the solution conformation of 2′-deoxyadenosine- and 2′-deoxyguanosine-3′,5′-bisphosphates, 3 and 4, d(pNp), as well as their Zn2+/Mg2+ binding sites and binding-modes (i.e. inner- vs. outer-sphere coordination), acidity constants, stability constants of their Zn2+/Mg2+ complexes, and their species distribution. Analogues 3 and 4, in solution, adopted a predominant Southern ribose conformer (ca. 84%), gg conformation around C4′–C5′ and C5′–O5′ bonds, and glycosidic angle in the anti-region (213–270°). 1H- and 31P-NMR experiments indicated that Zn2+/Mg2+ ions coordinated to P5′ and P3′ groups of 3 and 4 but not to N7 nitrogen atom. Analogues 3 and 4 formed ca. 100-fold more stable complexes with Zn2+vs. Mg2+-ions. Complexes of 3 and 4 with Mg2+ at physiological pH were formed in minute amounts (11% and 8%, respectively) vs. Zn2+ complexes (46% and 44%). Stability constants of Zn2+/Mg2+ complexes of analogues 3 and 4 (log KMML = 4.65–4.75/2.63–2.79, respectively) were similar to those of the corresponding complexes of ADP and GDP (log KMML = 4.72–5.10/2.95–3.16, respectively). Based on the above findings, we hypothesized that the unexpectedly low log K values of Zn2+-d(pNp) as compared to Zn2+-NDP complexes, are possibly due to formation of outer-sphere coordination in the Zn2+-d(pNp) complex vs. inner-sphere in the NDP-Zn2+ complex, in addition to loss of chelation to N7 nitrogen atom in Zn2+-d(pNp). Indeed, explicit solvent molecular dynamics simulations of 1 and 3 for 100 ns supported this hypothesis.

Graphical abstract: Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn2+-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate

Back to tab navigation

Supplementary files

Publication details

The article was received on 08 Jan 2015, accepted on 03 Mar 2015 and first published on 06 Mar 2015


Article type: Paper
DOI: 10.1039/C5DT00080G
Author version
available:
Download author version (PDF)
Citation: Dalton Trans., 2015,44, 7305-7317
  •   Request permissions

    Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn2+-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate

    A. H. Sayer, E. Blum, D. T. Major, A. Vardi-Kilshtain, B. Levi Hevroni and B. Fischer, Dalton Trans., 2015, 44, 7305
    DOI: 10.1039/C5DT00080G

Search articles by author

Spotlight

Advertisements